第十四章核苷酸代谢.ppt

Radioisotope tracer experiments revealed the origins of the atoms in the purine and pyrimidine rings. Purine and pyrimidine bases can be reconverted to nucleotides via the salvage pathway De novo purine nucleotide synthesis: the base assembles on the ribose phosphate; IMP is first nucleotide synthesized. The biosynthesis of AMP and GMP is regulated mainly by sequential feedback inhibition (no covalent regulation) All dNDPs are derived from NDPs via the catalysis of a common ribonucleotide reductase likely via a 3`-ribonucleotide radical intermediate. Summary Purine nucleotides are synthesized from PRPP, Gln, Gly, N10-formyl H4 folate, HCO3-, Asp through the de novo pathway. Pyrimidine nucleotides are synthesized using HCO3-, Gln, Asp, and PRPP. De novo synthesis of nucleotides are regulated via feedback inhibition (no covalent modifications yet revealed). Deoxyribonucleotides are derived from ribonucleotides at the NDP level, with the catalysis of ribonucleotide reductase, which contains a chain of electron carriers, uses free radicals, and be regulated for both substrate specificity and overall enzymatic activities. The dTMP molecule is derived from dUMP by thymidylate synthase, an enzyme using N5, N10-methylene-tetrahydrofolate as the donor of both one-carbon unit and electrons. Degradation of purines and pyrimidines produces uric acid and citric acid cycle intermediate/fatty acid synthesis precursor, respectively. Purine and pyrimidine bases can be reused via the salvage pathway. Many cancer chemotherapeutic drugs (e.g., azaserine, acivicin, fluorouracil, and methotrexate) inhibits enzymes in the nucleotide biosynthetic pathways. IMP is first formed before being converted to AMP and GMP. Biotin is not needed! 7 and 8 are catalyzed by one bifunctional enzyme 10 and 11 are catalyzed by one bifunctional enzyme By-product of His biosynthesis ＊AMP → ADP → ATP 与 GMP → GDP → GTP的转化 ⒉ 从头合成的调节 单体 二聚体 （有活性） （无活性） IMP AMP GMP PRPP （＋） （＋） AMP an